title: Resveratrol suppresses PAI-1 gene expression in a human in vitro model of inflamed adipose tissue.
abstract: Increased plasminogen activator inhibitor-1 (PAI-1) levels are associated with a number of pathophysiological complications; among them is obesity. Resveratrol was proposed to improve obesity-related health problems, but the effect of resveratrol on PAI-1 gene expression in obesity is not completely understood. In this study, we used SGBS adipocytes and a model of human adipose tissue inflammation to examine the effects of resveratrol on the production of PAI-1. Treatment of SGBS adipocytes with resveratrol reduced PAI-1 mRNA and protein in a time- and concentration-dependent manner. Further experiments showed that obesity-associated inflammatory conditions lead to the upregulation of PAI-1 gene expression which was antagonized by resveratrol. Although signaling via PI3K, Sirt1, AMPK, ROS, and Nrf2 appeared to play a significant role in the modulation of PAI-1 gene expression under noninflammatory conditions, those signaling components were not involved in mediating the resveratrol effects on PAI-1 production under inflammatory conditions. Instead, we demonstrate that the resveratrol effects on PAI-1 induction under inflammatory conditions were mediated via inhibition of the NF κ B pathway. Together, resveratrol can act as NF κ B inhibitor in adipocytes and thus the subsequently reduced PAI-1 expression in inflamed adipose tissue might provide a new insight towards novel treatment options of obesity.
authors.affiliation: Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Zagotta
authors.forename: Elitsa Y
authors.initials: EY
authors.lastname: Dimova
authors.forename: Jan-Bernd
authors.initials: JB
authors.lastname: Funcke
authors.forename: Martin
authors.initials: M
authors.lastname: Wabitsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Kietzmann
authors.forename: Pamela
authors.initials: P
authors.lastname: Fischer-Posovszky
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000473:pathology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000473:pathology; D005877:Gigantism / Q000235:genetics / Q000473:pathology; D006330:Heart Defects, Congenital / Q000235:genetics / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics*; D008607:Intellectual Disability / Q000235:genetics / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D017077:Culture Media, Conditioned; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013267:Stilbenes; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1; D000077185:Resveratrol